Potential for improved detection of bovine tuberculosis by targeting combined blood biomarkers in multi-test algorithms

Authors: SRIDHARA, ARCHANA - Chembio Diagnostic Systems, Inc; JOHNATHAN-LEE, ASHLEY - Chembio Diagnostic Systems, Inc; ELAHI, RUBYAT - Chembio Diagnostic Systems, Inc; SIKAR-GANG, ALINA - Chembio Diagnostic Systems, Inc; LAMBOTTE, PAUL - Chembio Diagnostic Systems, Inc; ESFANDIARI, JAVAN - Chembio Diagnostic Systems, Inc; DE JUAN, LUCIA - Complutense University Of Madrid (UCM); GORTAZAR, CHRISTIAN - University Of Castilla-La Mancha(UCLM); JONES, GARETH - Animal And Plant Health Agency; VORDERMEIER, H. MARTIN - Animal And Plant Health Agency; Marpe, Breanne; Thacker, Tyler; Palmer, Mitchell; WATERS, W. RAY - US Department Of Agriculture (USDA); LYACHCHENKO, KONSTANTIN - Chembio Diagnostic Systems, Inc

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/6/2022
Publication Date: 4/16/2022
Citation: Sridhara, A.A., Johnathan-Lee, A., Elahi, R., Sikar-Gang, A., Lambotte, P., Esfandiari, J., De Juan, L., Gortazar, C., Jones, G., Vordermeier, H., Marpe, B.N., Thacker, T.C., Palmer, M.V., Waters, W., Lyachchenko, K.P. 2022. Potential for improved detection of bovine tuberculosis by targeting combined blood biomarkers in multi-test algorithms. Veterinary Immunology and Immunopathology. Volume 248, June 2022, 110419. https://doi.org/10.1016/j.vetimm.2022.110419.
DOI: https://doi.org/10.1016/j.vetimm.2022.110419

Interpretive Summary: One obstacle to eradication of tuberculosis from cattle is the lack of rapid, accurate diagnostic tests. Historically, the diagnosis of bovine tuberculosis has relied on tuberculin skin testing (TST). The TST requires multiple days and multiple animal handling events, and has moderate accuracy. One approach is to use multiple tests to increase accuracy. We examined the use of rapid blood-based tests as adjuncts to traditional diagnostic tests. The use of multiple tests increased the ability of the assays to identify infected cattle. The reliable identification of infected cattle would allow the removal of only infected animals from a herd, rather than relying on whole herd depopulation, which is the currently preferred disposition of herds with even a single infected animal. Whole herd depopulation is costly to both producers and USDA, and can be emotionally taxing on herd owners. This would reduce the euthanasia of normal, non-infected cattle, expedite the eradication effort, and encourage positive relationships between producers and USDA officials.

Technical Abstract: Bovine tuberculosis (bTB) control programs can be improved by combined use of tests for humoral and cell-mediated immune responses targeting multiple biomarkers of Mycobacterium bovis. To further the diagnostic benefits of this approach, we evaluated sera from bTB-infected and non-infected cattle from the US and Spain for the presence of M. bovis antigen, IgM and/or IgG antibodies to MPB70/MPB83 fusion antigen using Dual Path Platform (DPP) technology in conjunction with tuberculin skin tests (TST) or interferon-gamma release assays (IGRA). When TST was complemented with detection of IgM and IgG antibodies, the diagnostic sensitivity increased from 85.4% to 95.1% in the US and from 64.2% to 81.5% in Spain. Likewise, adding the DPP assays enhanced IGRA diagnostic sensitivity from 82.7% to 93.8% in Spain. Detection of circulating M. bovis antigen showed added value when used in combination with the DPP antibody assays but it was limited when analyzed in the context of TST or IGRA results. Present findings support the benefits of a multi-test approach for the ante-mortem diagnosis of bTB in cattle.